The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response

[sharon sanders]

The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response

Daniel A. Muruve^1,⁵, Virginie P?trilli^3,⁵, Anne K. Zaiss², Lindsay R. White¹, Sharon A. Clark¹, P. Joel Ross⁴, Robin J. Parks⁴ & Jurg Tschopp³

1. Department of Medicine,
2. Biochemistry and Molecular Biology, University of Calgary, Alberta T2N 4N1, Canada
3. Department of Biochemistry, University of Lausanne, Epalinges, Switzerland
4. Molecular Medicine Program, Ottawa Health Research Institute, Ottawa, Ontario K1Y 4E9, Canada
5. These authors contributed equally to this work.

Correspondence to: Jurg Tschopp³ Correspondence and requests for materials should be addressed to J.T. (Email: Jurg.Tschopp@unil.ch).

Top of pageThe innate immune system recognizes nucleic acids during infection and tissue damage. Whereas viral RNA is detected by endosomal toll-like receptors (TLR3, TLR7, TLR8) and cytoplasmic RIG-I and MDA5, endosomal TLR9 and cytoplasmic DAI bind DNA¹, resulting in the activation of nuclear factor-B and interferon regulatory factor transcription factors. However, viruses also trigger pro-inflammatory responses², which remain poorly defined. Here we show that internalized adenoviral DNA induces maturation of pro-interleukin-1 in macrophages, which is dependent on NALP3 and ASC, components of the innate cytosolic molecular complex termed the inflammasome. Correspondingly, NALP3- and ASC-deficient mice display reduced innate inflammatory responses to adenovirus particles. Inflammasome activation also occurs as a result of transfected cytosolic bacterial, viral and mammalian (host) DNA, but in this case sensing is dependent on ASC but not NALP3. The DNA-sensing pro-inflammatory pathway functions independently of TLRs and interferon regulatory factors. Thus, in addition to viral and bacterial components or danger signals in general, inflammasomes sense potentially dangerous cytoplasmic DNA, strengthening their central role in innate immunity.


http://www.nature.com/nature/journal...ture06664.html

[sharon sanders]

Re: The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response






Fig. 1. NALP3 inflammasome: 700 kDa five-protein complex consisting of NALP3, the adaptor protein ASC, the caspase recruiting protein cardinal, and a dimmer of caspase-1. The inflammasome activates caspase-1 which then converts proIL-1? to active IL-1?

http://ndt.oxfordjournals.org/cgi/content/full/gfl226?ijkey=kiPpN8tiA17feq1&keytype=ref